Comparative responses to alpha ,beta -methylene-ATP in cat pulmonary, mesenteric, and hindquarter vascular beds

Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112 Responses to the P2X-purinoceptor agonist , -methylene-ATP ( , -MeATP) were investigated in the pulmonary, hindquarter, and mesenteric vascular beds in the cat. Under constant-flow conditions, injections of , -MeATP caused dose-related increases in perfusion pressure in the pulmonary and hindquarter beds and a biphasic response in the mesenteric circulation. In the pulmonary vascular bed, the order of potency was , -MeATP > U-46619 > angiotensin II, whereas, in the hindquarters, the order of potency was angiotensin II > U-46619 > , -MeATP. The order of potency was similar in the hindquarter and mesenteric beds when the pressor component of the response to , -MeATP was compared with responses to angiotensin II and U-46619. The P2X-receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid attenuated the pressor response to , -MeATP in the hindquarter circulation and the pressor component in the mesenteric vascular bed. Pressor responses to , -MeATP were not altered by cyclooxygenase, -adrenergic, or angiotensin AT 1 antagonists. These data show that , -MeATP has potent pressor activity in the pulmonary circulation, where it was 100-fold more potent than angiotensin II. In contrast, , -MeATP had modest pressor activity in the systemic bed, where it was 1,000-fold less potent than angiotensin II. These data suggest that responses to , -MeATP are dependent on the vascular bed studied and may be dependent on the density of P2X receptors in the vascular bed. vasoconstrictor; pulmonary and peripheral vascular bed; pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid